The goal of this grant application is to test the hypothesis that resuscitation from cardiac arrest is limited by pulmonary vasoconstriction and that inhalation of nitric oxide during resuscitation from either ventricular fibrillation or pulseless electrical activity/asystole cardiac arrest will increase blood flow caused by chest compressions and improve short-term survival. The efficacy of chest compressions in generating forward systemic blood flow is poor, often estimated at 10-25% of normal cardiac output. Yet. the question, 'How does pulmonary vascular resistance affect forward blood flow during CPR?'has not been been answered by the resuscitation research community. Any constriction to blood flow in the pulmonary circulation during chest compressions will limit blood flow in the systemic circulation and dilation of the pulmonary vessels should lead to an increase in blood flow during chest compressions. Based on these ideas, we propose the following specific aims. Specific Aim 1: Cardiac arrest secondary to ventricular fibrillation. We hypothesize: that poorly oxygenated blood returning to the lungs causes an increase in pulmonary vascular resistance which in turn causes a decrease in blood flow during chest compressions. Further, delivery of inhaled nitric oxide, 20 ppm, during resuscitation, will decrease pulmonary vascular resistance, increase blood flow and improve survival. Specific Aim 2: Cardiac arrest secondary to respiratory arrest. We hypothesize that an increase in pulmonary vascular resistance occurs secondary to both hypoxia and poorly oxygenated mixed venous blood which in turn causes a decrease in blood flow during chest compressions. Further, inhaled nitric oxide, 20 ppm, will decrease pulmonary vascular resistance, improve blood flow during chest compressions and improve survival. We believe that manipulating the pulmonary vasculature will lead to a paradigm shift in resuscitation protocols and lead to an increased survival from cardiac arrest. PUBLIC HEALTH RELEVANCE: Cardiac Arrest in the pre-hospital setting is a leading cause of death in the United States. Chest compressions are the only accepted means of providing blood flow until the heart can be made to contract again. We hypothesize that constriction of the arteries in the lung limit the blood flow generated by chest compressions and that dilating these blood vessels with drugs delivered to the lungs by inhalation will improve blood flow generated by chest compressions and ultimately improve survival from cardiac arrest.